The candidate plans to become an independent, established investigator in pediatric bone and mineral metabolism in a setting where clinical exposure will foster scientific curiosity applicable to a laboratory setting. The research addresses certain observations in patients with metabolic bone disease regarding the relationship between vitamin D metabolism and phosphate transport. The experiments systematically evaluate mitochondrial metabolism in animal models of defective PO4 transport. Examination of mitochondrial PO4 content and transports, and monitoring of biochemical events during mitochondrial respiration will be performed using classical methods. 1AlphaOHlase activity will be determined in association with mitochondrial respiration and with alterations in extramitochondrial ionic milieu. Chronic regulation of 1AlphaOHlase activity will be investigated with respect to alterations in PO4 transport and intracellular ionic milieu. We seek a mechanism with shared pathogenetic elements to explain the observed associated defects in PO4 transport and vitamin D metabolism. Yale University is a major scientific center attached to the Yale-New Haven Hospital. The sponsor will be of invaluable assistance in carrying out the proposed projects in a major area of his interest, mitochondrial biochemistry. His expertise and direct oversight of the project will provide an incomparable environment for training.